The overall objective is to understand the neuroanatomical organization of areas of the nervous system responsible for the control of food intake and body weight regulation. Although it has been known for some time that damage to certain areas of the hypothalamus can lead to obesity in an otherwise normal experimental animal, the neuroanatomical organization of these areas, which include the ventromedial (VMN), arcuate (ARC) and dorsal premammillary (DP) nuclei, is not well understood. Recent biochemical evidence based on chemical stimulation and measurement of catecholamine levels has also implicated the paraventricular nucleus (PVN) and the median eminence (ME). The present series of experiments are aimed at 1) elucidation of hypothalamic organization in normal rats and 2) determination of possible anatomical and biochemical abnormalities in the brains of genetically obese rats. Normal cytoarchitectonic features as well as neural connections of VMN, ARC, DP, PVN and ME will be studied. The techniques utilized will include Golgi, thionin, protargol and neurosecretory staining. Investigation of neural connections will employ the autoradiographic technique for tracing efferent connections and the horseradish peroxidase technique for tracing afferent connections. Catecholamine levels will be measured to determine possible differences based on 1) sex, 2) hormonal levels, 3) brainstem cell bodies which send terminals to the hypothalamus. Three types of animals will be used: (1) normal animals of the Sprague-Dawley strain, (2) genetically obese animals of the Zucker strain, and (3) normal animals of the Zucker strain which carry no genes for obesity. In humans a relationship exists between obesity and certain diseases. Elucidation of the neuroanatomical pathways involved in the control of food intake and body weight regulation as well as demonstration of abnormalities in the brains of genetically obese animals will be of use in therapeutic approaches to obesity.